Investigation of the effect of insulin on uridine levels in rats

Uridine, a pyrimidine nucleoside, is an endogenous compound detected both in free form and in the form of mono-, di- and trinucleotides and nucleotide sugars (UDP-glucose and UDP-galactose). It is also an important part of ribonucleic acid (RNA) and plays critical roles in many physiological functions like biosynthesis of glycogen and glycosylation of proteins and lipids. With the identification of nucleotide receptors, role of pyrimidine nucleosides (pyrimidinergic transmission) in the communication of nerve cells has also been proposed. The mechansim for the uptake of uridine by the cells of body, after being released from the RNA as a food ingredient, is yet unknown. In in-vitro experiments, the transport and uptake of uridine by the tissues has been proposed to be associated with hormones (insulin, glucagon) so that uridine can be incorporated in nucleotides and nucleic acids. The aim of our experiment was to determine the effects of insulin on levels of uridine in rats. Therefore, firstly, levels of glucose and uridine were investigated during fasting and in fully-fed animals. Blood samples from rats inserted with arterial cannulas were obtained in fasting state after 24 hour food restriction, and then at certain time points 1 hour following feeding in order to investigate time-dependent changes in glucose and uridine levels. In a separate group of animals, serum insulin levels were analyzed once during fasting state and 2 hours after feeding has started. In a second protocol, serum uridine levels were determined after intraperitoneal injection of different doses of insulin. Following insulin injection, a catheter was placed in the femoral artery and blood samples were collected at different time intervals and were then processed for measurement of levels of uridine, glucose and insulin. Finally, the association of cellular glucose uptake in the decreased serum uridine concentrations was investigated using hyperinsulinemic-euglycemic clamp method. Our findings showed that serum uridine concentrations were decreased at the time of insulin increase in fully-fed animals, subcutaneous insulin administration decreased serum uridine in a dose- and time-dependent manner and that such changes in uridine concentrations were not associated with cellular uptake of glucose. Data obtained in our study suggest, for the first time in the literature, that insulin stimulates cellular uptake of uridine and this process is independent from that of glucose. Further studies are needed in order to reveal molecular mechanisms of uridine uptake. Key words: Uridine, Insulin, hyperinsulinemic-euglycemic clamp, cellular uptake